We constructed three separate three-dimensional (3-D) models from serial high voltage electron micrographs (HVEM) of five human keratocytes. The serial micrographs were digitized using HVEM-3D software and a digitizing tablet on a personal computer system. After the models were constructed, we added surface and volume data using another computer program, SYNU. Hard copies of selected orientations of the model were obtained with a laser printer, by color photographs of the computer monitor, by direct imaging from the computer file, or by video recording. The first model was constructed from 73 serial sections of two activated keratoconus keratocytes next to a break in Bowman's layer (BL). Two adjacent keratocytes from the same cornea, but located away from disruptions in BL, made up the second model. The third model was created from approximately 106 serial sections of a normal human keratocyte cultured in an attached collagen gel. Examination of these 3-D models created from HVEM micrographs showed striking differences in keratocyte morphology and cell/matrix interactions related to corneal disease.